CSNK1G3 (casein kinase 1 gamma 3) is a serine/threonine-protein kinase that phosphorylates acidic protein substrates and participates in multiple cellular pathways including Wnt signaling and synaptic transmission 1. The protein localizes to the nucleus, plasma membrane, and cytoplasm, where it regulates canonical Wnt signaling, endocytosis, and signal transduction processes. Mechanistically, CSNK1G3 functions as a nodal kinase in cancer signaling networks. RNAi screening identified CSNK1G3 as an Akt-cooperating kinase; CSNK1G3 inhibition combined with Akt inhibition enhanced cancer cell killing and reduced phosphorylation of Akt Ser-473 and ribosomal protein S6 2. In triple-negative breast cancer, the curcumin derivative N17 exerts anti-cancer effects by targeting CSNK1G3 to suppress p-AKT(S473) phosphorylation, triggering apoptosis and inhibiting epithelial-mesenchymal transition 3. Clinically, CSNK1G3 alterations occur as fusion partners in cancer; a CSNK1G3-ALK fusion was identified in lung squamous cell carcinoma and responded to ALK tyrosine kinase inhibitors with durable disease control exceeding 30 months 4. Additionally, CSNK1G3 expression is dysregulated in vitiligo, with significantly reduced mRNA levels in depigmented lesional skin compared to non-lesional skin in an autoimmune mouse model 5. CSNK1G3 also shows signatures of positive natural selection in Taiwanese Han populations with associations to metabolic traits 6.