EFCAB7 is a ciliary calcium-binding protein that functions as a critical component of the EvC complex, which positively regulates Hedgehog signaling during development 1. EFCAB7 anchors the EVC-EVC2 complex at the base of primary cilia, creating a signaling microdomain essential for GLI2 activation 1. Loss-of-function variants in EFCAB7 impair ciliary localization of the EVC-EVC2 complex and disrupt Shh/Gli pathway activity, leading to transcriptional downregulation of cardiac development genes 2. Clinically, EFCAB7 mutations cause nonsyndromic postaxial polydactyly through disrupted Hedgehog signaling during limb formation 3. A splicing variant (c.683-1G>C) causes Tetralogy of Fallot, establishing EFCAB7 as a causative gene for congenital heart disease by impairing cardiac septation 2. EFCAB7 may also modify phenotypes in Ellis-van Creveld syndrome when co-inherited with EVC/EVC2 mutations 4. Notably, EFCAB7 is dispensable for male fertility in mice 5, and recent evidence suggests EFCAB7 upregulation promotes hepatocellular carcinoma progression through PARK7 interaction 6. These findings establish EFCAB7's primary role in ciliary-dependent developmental signaling with emerging implications in cancer biology.