ANKFN1 (ankyrin repeat and fibronectin type III domain containing 1) is a protein containing ankyrin repeat and fibronectin type III domains with emerging roles in both normal physiology and disease. While its precise molecular function remains incompletely characterized, ANKFN1 appears involved in cellular regulation processes, including mitotic spindle orientation and cell polarity establishment based on GO annotations. In hepatocellular carcinoma (HCC), ANKFN1 is significantly upregulated in tumor tissues and promotes disease progression through the MEK1/2-ERK1/2 signaling pathway, which activates the cyclin D1/Cdk4/Cdk6 pathway to drive G1/S cell cycle transition and suppress apoptosis 1. ANKFN1 upregulation correlates with cirrhosis, elevated alpha-fetoprotein levels, and poor prognosis, with knockdown studies demonstrating its necessity for HCC cell proliferation, migration, invasion, and metastasis 1. Genetic studies reveal ANKFN1 associations with multiple complex traits and conditions. Genome-wide association studies identified ANKFN1 variants associated with cannabis use and cannabis dependence 23, and with multiple sclerosis susceptibility 4. HBV integration events near ANKFN1 have been identified in intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma, suggesting involvement in HBV-induced hepatocarcinogenesis 5. An 11-gene signature including ANKFN1 predicts immunotherapy response in bladder cancer 6. Additionally, chr17 microdeletion encompassing ANKFN1 and NOG causes symphalangism spectrum disorder with skeletal and auditory manifestations 7. ANKFN1 represents a potential therapeutic target in HCC with possible broader relevance to multiple disease pathways.