DISP1 is a twelve transmembrane domain transporter that functions as a critical regulator of Hedgehog (Hh) signaling by mediating the secretion and extracellular transport of cholesterol-modified Sonic hedgehog (Shh) proteins 1. The protein contains two extracellular domains that engage with Hh ligand and contains cholesterol-binding sites within its transmembrane regions, suggesting a transport-like mechanism 1. DISP1 exhibits dual functionality: it is required for Shh secretion from source cells and enables subsequent long-range Shh transport through tissues, with inhibition of DISP1 preventing Shh secretion and reducing signaling range 2. Clinically, DISP1 variants are associated with a spectrum of midline craniofacial malformations, particularly holoprosencephaly (HPE). Monoallelic loss-of-function variants cause minor HPE forms including orofacial clefts, solitary median maxillary central incisor, and nasal pyriform aperture stenosis, while severe HPE typically involves biallelic variants or oligogenic inheritance with other HPE-linked genes 3. DISP1 has also been implicated in congenital diaphragmatic hernia (CDH) pathogenesis through its expression in embryonic diaphragm tissue during critical developmental stages 4. Additionally, DISP1 variants show associations with acute kidney injury (AKI) susceptibility, with differential DISP1 expression observed in proximal tubular cells and loop of Henle tissue from AKI patients 5.