ANKHD1 (ankyrin repeat and KH domain containing 1) functions as a scaffolding protein that plays crucial roles in cell cycle regulation and proliferation control. The protein contains multiple ankyrin repeat domains that mediate protein-protein interactions and a K-homology (KH) domain that binds RNA or single-stranded DNA 1. ANKHD1 operates through several key mechanisms: it directly binds to and represses the p21 promoter, promoting cell cycle progression 2; it interacts with the Cyclin D1/CDK4 pathway to enhance retinoblastoma phosphorylation and drive proliferation 3; and it regulates the Hippo signaling pathway by increasing YAP protein levels and inhibiting YAP phosphorylation 4. Additionally, ANKHD1 binds to specific tumor-suppressing miRNAs (miR-29a, miR-205, miR-196a) through its KH domain, leading to their suppression and subsequent upregulation of proliferative genes like CCND1 5. ANKHD1 is clinically significant as it is overexpressed in multiple cancer types including non-small-cell lung cancer, renal cell carcinoma, multiple myeloma, and colorectal cancer, where elevated expression correlates with poor prognosis, increased metastasis, and treatment resistance 146. The protein has also been implicated in autosomal dominant polycystic kidney disease and intellectual disability 37.