TTC21B encodes IFT139, a component of the intraflagellar transport-A (IFT-A) complex essential for retrograde ciliary transport and cilium assembly 1. The protein facilitates retrograde trafficking of IFT-B complexes and G protein-coupled receptors into cilia 2, and localizes at the ciliary base in developing podocytes but redistributes along microtubules in differentiated cells 1. TTC21B mutations cause nephronophthisis 12 (NPHP12), characterized by progressive cystic kidney disease, tubular basement membrane thickening, and interstitial fibrosis 34. Homozygous missense mutations, particularly p.P209L, cause focal segmental glomerulosclerosis (FSGS) with tubulointerstitial lesions and associated systemic features including hypertension and myopia 51. Heterozygous TTC21B variants act as genetic modifiers, increasing severity in compound heterozygous carriers and appearing enriched in kidney disease patients 5. TTC21B mutations also associate with short-rib thoracic dysplasias and represent a novel candidate gene in Bardet-Biedl syndrome, where mutations increase kidney failure risk 67. The gene contributes to biliary ciliopathy phenotypes 8. Importantly, both homozygous and heterozygous mutations can cause disease, with neonatal presentations possible 4, making genetic testing valuable for unexplained kidney disease across age groups.