KIF12 is a kinesin family motor protein that functions primarily as a negative regulator of hepatic lipogenesis. Its key mechanism involves serving as an adapter protein that facilitates ubiquitination and degradation of acetyl-CoA carboxylase 1 (ACC1) and pyruvate carboxylase (PC) by the E3 ligase COP1, with this adapter function dependent on its C-terminal proline-rich domain rather than its motor activity 1. KIF12 also plays important roles during kidney development, with high expression in early nephrogenesis that decreases through development, suggesting involvement in establishing normal renal tubular epithelial cell function 2. Disease relevance is substantial: biallelic KIF12 mutations cause progressive familial intrahepatic cholestasis type 8 (PFIC8), characterized by elevated gamma-glutamyl transferase activity and variable progression from neonatal cholestasis to cirrhosis 34. KIF12-deficient hepatocytes show metabolic dysfunction-associated steatohepatitis (MASH)-like phenotypes with impaired hepatocyte polarity 15. Clinically, KIF12 mutations account for approximately 28% of genetically-identified neonatal cholestasis cases, with genetic diagnosis improving from 18.2% pre-2010 to 35.5% post-2010 4. Disease severity varies among genotypes without clear genotype-phenotype correlation, ranging from asymptomatic enzyme elevation to early-onset liver cirrhosis requiring transplantation 3.