C12orf43 is a poorly characterized gene located on chromosome 12 that plays a role in regulating the Wnt signaling pathway during early development. While the specific molecular mechanism remains incompletely defined, C12orf43 appears to be involved in controlling Wnt-β-catenin signaling, similar to the related protein Custos, which modulates β-catenin nuclear translocation during embryogenesis 1. Genetically, C12orf43 has emerged as a disease-associated locus, particularly in cardiovascular disease. The SNP rs2258287 in the C12orf43 region shows significant association with coronary artery disease (CAD) risk in Pakistani populations, with carriers displaying unfavorable lipid profiles including elevated LDL-cholesterol and triglycerides, and reduced HDL-cholesterol 23. A genome-wide association study identified suggestive CAD association at the HNF1A-C12orf43 locus 4. Additionally, C12orf43 was identified as part of a gene signature predicting radiotherapy resistance in colorectal cancer, associated with tumor mutation burden and microsatellite instability 5. These findings suggest C12orf43 functions at the intersection of developmental signaling and disease pathogenesis, though further functional studies are needed to clarify its precise molecular role in both Wnt signaling and disease susceptibility.