diff --git a/.changes/next-release/bugfix-AWSSDKforJavav2-38866e6.json b/.changes/next-release/bugfix-AWSSDKforJavav2-38866e6.json
new file mode 100644
index 000000000000..f6df85f9d6a3
--- /dev/null
+++ b/.changes/next-release/bugfix-AWSSDKforJavav2-38866e6.json
@@ -0,0 +1,6 @@
+{
+    "type": "bugfix",
+    "category": "AWS SDK for Java v2",
+    "contributor": "",
+    "description": "Fix DynamoDB Enhanced Client immutable class introspection fails for \"is\" prefix fields. Fixes [#4446](https://github.com/aws/aws-sdk-java-v2/issues/4446)."
+}
diff --git a/services-custom/dynamodb-enhanced/src/main/java/software/amazon/awssdk/enhanced/dynamodb/internal/immutable/ImmutableIntrospector.java b/services-custom/dynamodb-enhanced/src/main/java/software/amazon/awssdk/enhanced/dynamodb/internal/immutable/ImmutableIntrospector.java
index c7095dd38b05..ca2cc9005fd9 100644
--- a/services-custom/dynamodb-enhanced/src/main/java/software/amazon/awssdk/enhanced/dynamodb/internal/immutable/ImmutableIntrospector.java
+++ b/services-custom/dynamodb-enhanced/src/main/java/software/amazon/awssdk/enhanced/dynamodb/internal/immutable/ImmutableIntrospector.java
@@ -180,6 +180,14 @@ private String normalizeSetterName(Method setter) {
             return Character.toLowerCase(setterName.charAt(3)) + setterName.substring(4);
         }
 
+        if (setterName.length() > 2
+            && Character.isUpperCase(setterName.charAt(2))
+            && setterName.startsWith(IS_PREFIX)
+            && isSetterMethodBoolean(setter)) {
+
+            return Character.toLowerCase(setterName.charAt(2)) + setterName.substring(3);
+        }
+
         return setterName;
     }
 
@@ -208,6 +216,11 @@ private boolean isMethodBoolean(Method method) {
         return method.getReturnType() == boolean.class || method.getReturnType() == Boolean.class;
     }
 
+    private boolean isSetterMethodBoolean(Method setter) {
+        return setter.getParameterCount() == 1 && 
+               (setter.getParameterTypes()[0] == boolean.class || setter.getParameterTypes()[0] == Boolean.class);
+    }
+
     private Optional<Method> extractBuildMethod(Map<String, Method> indexedBuilderMethods, Class<?> immutableClass) {
         Method buildMethod = indexedBuilderMethods.get(BUILD_METHOD);
 
diff --git a/services-custom/dynamodb-enhanced/src/test/java/software/amazon/awssdk/enhanced/dynamodb/TableSchemaImmutableIsPrefixTest.java b/services-custom/dynamodb-enhanced/src/test/java/software/amazon/awssdk/enhanced/dynamodb/TableSchemaImmutableIsPrefixTest.java
new file mode 100644
index 000000000000..229511d7b164
--- /dev/null
+++ b/services-custom/dynamodb-enhanced/src/test/java/software/amazon/awssdk/enhanced/dynamodb/TableSchemaImmutableIsPrefixTest.java
@@ -0,0 +1,162 @@
+/*
+ * Copyright Amazon.com, Inc. or its affiliates. All Rights Reserved.
+ *
+ * Licensed under the Apache License, Version 2.0 (the "License").
+ * You may not use this file except in compliance with the License.
+ * A copy of the License is located at
+ *
+ *  http://aws.amazon.com/apache2.0
+ *
+ * or in the "license" file accompanying this file. This file is distributed
+ * on an "AS IS" BASIS, WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either
+ * express or implied. See the License for the specific language governing
+ * permissions and limitations under the License.
+ */
+
+package software.amazon.awssdk.enhanced.dynamodb;
+
+import static org.assertj.core.api.Assertions.assertThat;
+
+import org.junit.Test;
+import software.amazon.awssdk.enhanced.dynamodb.mapper.annotations.DynamoDbImmutable;
+import software.amazon.awssdk.enhanced.dynamodb.mapper.annotations.DynamoDbPartitionKey;
+
+/**
+ * Tests that TableSchema.fromImmutableClass() works correctly with immutable classes
+ * that have fields using "is" prefix.
+ */
+public class TableSchemaImmutableIsPrefixTest {
+
+    // Test class for boolean fields with "is" prefix
+    @DynamoDbImmutable(builder = Car.Builder.class)
+    public static final class Car {
+        private final String licensePlate;
+        private final boolean isRusty;
+        private final boolean isImpounded;
+
+        private Car(Builder b) {
+            this.licensePlate = b.licensePlate;
+            this.isRusty = b.isRusty;
+            this.isImpounded = b.isImpounded;
+        }
+
+        @DynamoDbPartitionKey
+        public String licensePlate() {
+            return this.licensePlate;
+        }
+
+        public boolean isRusty() {
+            return this.isRusty;
+        }
+
+        public boolean isImpounded() {
+            return this.isImpounded;
+        }
+
+        public static final class Builder {
+            private String licensePlate;
+            private boolean isRusty;
+            private boolean isImpounded;
+
+            public Builder licensePlate(String licensePlate) {
+                this.licensePlate = licensePlate;
+                return this;
+            }
+
+            public Builder isRusty(boolean isRusty) {
+                this.isRusty = isRusty;
+                return this;
+            }
+
+            public Builder isImpounded(boolean isImpounded) {
+                this.isImpounded = isImpounded;
+                return this;
+            }
+
+            public Car build() {
+                return new Car(this);
+            }
+        }
+    }
+
+    @Test
+    public void fromImmutableClass_withIsPrefixBooleanSetters_shouldCreateSchemaSuccessfully() {
+        // This should work without exception
+        TableSchema<Car> schema = TableSchema.fromImmutableClass(Car.class);
+        
+        // Verify the schema was created successfully without exception
+        assertThat(schema).isNotNull();
+        assertThat(schema.itemType().rawClass()).isEqualTo(Car.class);
+        
+        // Verify all attributes are mapped correctly
+        assertThat(schema.attributeNames()).containsExactlyInAnyOrder(
+            "licensePlate", "rusty", "impounded"
+        );
+    }
+
+    // Test class for non-boolean fields with "is" prefix
+    @DynamoDbImmutable(builder = Vehicle.Builder.class)
+    public static final class Vehicle {
+        private final String licensePlate;
+        private final String isModel;
+        private final Integer isYear;
+
+        private Vehicle(Builder b) {
+            this.licensePlate = b.licensePlate;
+            this.isModel = b.isModel;
+            this.isYear = b.isYear;
+        }
+
+        @DynamoDbPartitionKey
+        public String licensePlate() {
+            return this.licensePlate;
+        }
+
+        public String isModel() {
+            return this.isModel;
+        }
+
+        public Integer isYear() {
+            return this.isYear;
+        }
+
+        public static final class Builder {
+            private String licensePlate;
+            private String isModel;
+            private Integer isYear;
+
+            public Builder licensePlate(String licensePlate) {
+                this.licensePlate = licensePlate;
+                return this;
+            }
+
+            public Builder isModel(String isModel) {
+                this.isModel = isModel;
+                return this;
+            }
+
+            public Builder isYear(Integer isYear) {
+                this.isYear = isYear;
+                return this;
+            }
+
+            public Vehicle build() {
+                return new Vehicle(this);
+            }
+        }
+    }
+
+    @Test
+    public void fromImmutableClass_withIsPrefixNonBooleanFields_shouldNotNormalizeIsPrefix() {
+        TableSchema<Vehicle> schema = TableSchema.fromImmutableClass(Vehicle.class);
+        
+        // Verify the schema was created successfully
+        assertThat(schema).isNotNull();
+        assertThat(schema.itemType().rawClass()).isEqualTo(Vehicle.class);
+        
+        // Verify non-boolean "is" prefix fields are not normalized
+        assertThat(schema.attributeNames()).containsExactlyInAnyOrder(
+            "licensePlate", "isModel", "isYear"
+        );
+    }
+}