ANKRD6 (ankyrin repeat domain 6) is a mammalian planar cell polarity (PCP) protein that functions as a homolog of Drosophila diego 1. The protein contains six ankyrin repeats and two coiled-coil regions that serve as binding domains 2. ANKRD6 recruits casein kinase I epsilon (CKI-epsilon) to the beta-catenin degradation complex containing AXN1/AXN2 and GSK3-beta, thereby suppressing canonical Wnt/β-catenin signaling while promoting WNT/PCP pathway activation 3. This dual regulatory role involves phosphorylating beta-catenin to inhibit Wnt/β-catenin-mediated transcription 1. During development, ANKRD6 is prominently expressed in the developing brain and is asymmetrically localized in inner ear sensory organ cells, where loss of ANKRD6 causes planar cell polarity defects 41. ANKRD6 loss-of-function studies in mice show increased canonical Wnt signaling, confirming its inhibitory role 1. Clinically, ANKRD6 overexpression associates with poor prognosis in gastric and colon adenocarcinomas, correlating with epithelial-mesenchymal transition markers and metastatic potential 56. ANKRD6 genetic variants influence muscle strength and physical activity responses in humans 7, indicating broader physiological roles beyond PCP signaling.