CIROP (ciliated left-right organizer metallopeptidase) is a putative metalloproteinase essential for establishing left-right asymmetry during vertebrate embryogenesis 1. Specifically expressed in the ciliated left-right organizer (LRO), CIROP functions downstream of leftward nodal flow but upstream of DAND5, the first asymmetrically expressed gene in this developmental pathway 1. CIROP belongs to a conserved genetic module with DAND5, PKD1L1, and MMP21 that evolved specifically in vertebrate species harboring motile cilia in their LRO 2. The protein localizes to the cytoplasm and possesses peptidase activity [GO annotations]. Loss-of-function mutations in CIROP cause autosomal recessive heterotaxy, a disorder characterized by abnormal organ positioning along the left-right axis 1. Clinical studies have identified 21 human patients with recessive CIROP mutations presenting with situs anomalies 1, and CIROP variants represent an important genetic cause of heterotaxy in consanguineous populations, contributing to a diagnostic yield of 42.1% in genetic testing panels 3. CIROP's essential role in left-right patterning is unique to humans and certain mammals, as the gene has been lost during evolution in multiple vertebrate lineages lacking motile cilia in their LROs 1.