NIPBL is a cohesin loading factor essential for genome organization and developmental processes. Its primary function involves forming a heterodimeric complex with MAU2 to load cohesin onto chr5, enabling DNA loop extrusion at rates up to 2.1 kilobase pairs per second 1. NIPBL activates the cohesin ATPase required for topological entrapment of sister DNAs and fuels dynamic loop extrusion, while also regulating conformational switches of the cohesin complex 2. Beyond cohesion, NIPBL recruits histone deacetylase to modulate gene expression through chr5 remodeling and interacts with transcriptional machinery to regulate developmental genes 3. During DNA damage response, NIPBL is recruited to double-strand breaks and UV-induced lesions through CBX3-, RNF8-, and RNF168-dependent mechanisms [UniProt]. NIPBL mutations cause Cornelia de Lange Syndrome (CdLS), accounting for >60% of cases and representing the only gene definitively associated with severe CdLS phenotypes 4. CdLS manifests as a multisystem developmental disorder featuring growth and developmental delays, craniofacial abnormalities, cardiac defects including ventricular septal defects, and gastrointestinal involvement 5. NIPBL interactions with BRD4 and other chr5 regulators are critical for proper genome folding during neural crest and cardiac development, with imbalances in cohesin activity disrupting these processes 6.