MID2 is an X-linked E3 ubiquitin ligase that plays critical roles in microtubule regulation and developmental processes 1. The protein localizes to cytoplasmic microtubular structures and contains conserved RBCC (RING finger, B-box, coiled coil) and B30.2 domains, with a fibronectin type III domain facilitating microtubule association 2. MID2 functions through multiple mechanisms: it mediates Lys-48-linked polyubiquitination of the microtubule-associated protein astrin at lysine 409, promoting astrin degradation during cytokinesis 3; it homo- and heterodimerizes with the related protein MID1 to tether the PP2A regulatory subunit Alpha 4 to microtubules 4; and it ubiquitinates LRRK2 to regulate its localization and proteasomal degradation in neurons. MID2 mutations are associated with X-linked intellectual disability, autism spectrum disorders, and neurodevelopmental abnormalities including microcephaly and brain malformations 5. MID2 dysregulation disrupts normal microtubule dynamics and cytokinesis, with mutations in MID2 implicated in developmental disorders affecting midline structures 1. Additionally, MID2 has been identified as a core hub gene associated with colorectal cancer pathogenesis through extracellular matrix and signaling pathway dysregulation 6.