NCKIPSD (NCK interacting protein with SH3 domain) is a cytoskeletal regulatory protein with multiple roles in actin dynamics and cellular processes. Functionally, NCKIPSD stimulates N-WASP-induced Arp2/3 complex activation independent of CDC42, promoting linear actin filament nucleation and microspike formation 1. The protein contains SH3 and proline-rich domains that facilitate interactions with dynamin and other endocytic proteins, linking endocytosis to actin dynamics 2. NCKIPSD plays important roles in stress fiber formation, sarcomere assembly, and angiogenesis through regulation of actin polymerization and cell adhesion. Genetically, NCKIPSD has been implicated in multiple complex diseases. A rare protein-coding variant (rs145562243) in NCKIPSD was identified as exome-wide significant for leprosy susceptibility (OR=4.35) in Han Chinese populations, highlighting involvement of endocytosis/autophagy pathways in disease pathogenesis 3. NCKIPSD was identified as a shared genetic risk gene for anxiety and stroke through genome-wide association meta-analysis 4, and as a candidate gene associated with hand osteoarthritis in transcriptome-wide association studies 5. Additionally, NCKIPSD was identified as a potential target in structural variant fine-mapping of anorexia nervosa loci 6. The gene's role in colon cancer metastasis has been suggested through its involvement in Rho signaling pathway regulation downstream of transgelin-PARP1 interactions 7.