LMBR1 encodes a putative membrane receptor that plays a critical role in vertebrate limb development through regulation of digit formation. The gene functions as a key regulator of limb patterning, where altered expression levels can cause reciprocal phenotypes: gain-of-function mutations lead to preaxial polydactyly (extra digits), while loss-of-function mutations cause oligodactyly (digit reduction) 1. LMBR1 is expressed within the zone of polarizing activity (ZPA) during limb development and appears to regulate Sonic Hedgehog (SHH) signaling 2. The gene undergoes extensive alternative splicing, generating multiple isoforms with potentially different functions 3. Disease-causing mutations include deletions affecting exon 4 that cause acheiropodia, characterized by severe bilateral limb amputations 4, and large duplications including the zone of polarizing activity regulatory sequence (ZRS) that cause triphalangeal thumb polysyndactyly syndrome 5. Recent studies suggest LMBR1 may also regulate osteogenesis through the BMP signaling pathway 6. The gene's critical role in limb development is conserved across vertebrates, with mutations consistently affecting digit number and limb formation patterns in humans, mice, and chickens 78.