TXNDC15 is a thioredoxin domain-containing transmembrane protein primarily localized to the endoplasmic reticulum that serves critical functions in ciliary biology and homeostasis 1. It acts as a positive regulator of ciliary hedgehog signaling and is essential for ciliogenesis 2. Mechanistically, TXNDC15 maintains transition zone (TZ) integrity at the ciliary base through its thioredoxin domain, which contains functionally important cysteine residues 1. Loss of TXNDC15 function impairs MKS module assembly and disrupts ciliary membrane protein localization 1. Clinically, TXNDC15 mutations cause Meckel syndrome 14 (MKS14), a perinatally lethal autosomal recessive ciliopathy characterized by occipital encephalocele, polycystic kidneys, and postaxial polydactyly 2, 3, 4, 5. Multiple pathogenic variants including loss-of-function mutations and compound heterozygous alleles have been identified in affected families 3, 4, 5. Beyond ciliopathies, emerging proteomic evidence suggests TXNDC15 may have ancestry-specific associations with Parkinson's disease risk in European populations and influences adiposity-related pathways 6, 7, though these associations require further mechanistic validation.