NUDCD2 (NudC domain containing 2) is an Hsp90 cochaperone protein that regulates multiple critical cellular processes through protein stabilization. Primary function: NUDCD2 stabilizes key client proteins including LIS1 (lissencephaly protein 1), myosin-9, and cohesin subunits by modulating Hsp90 chaperone activity 123. Mechanism: NUDCD2 complexes with Hsp90 to enhance its ATPase activity and promote stabilization of interaction partners. This cochaperone function localizes to centrosomes during interphase and spindle poles/kinetochores during mitosis 13. Disease relevance: Biallelic NUDCD2 variants cause a recognizable multiple malformation syndrome featuring midline brain hypoplasia, cholestasis, renal failure, profound hypotonia, and early death, with features suggestive of ciliopathy 4. NUDCD2 depletion destabilizes cohesin components and LIS1, leading to chromosome 5 defects, premature sister chr5 separation, and elevated cancer-associated pathways 53. Clinical significance: NUDCD2 alterations are associated with survival outcomes in head and neck squamous cell carcinoma 6. The protein appears downregulated in atherosclerotic vascular smooth muscle cell transformation 7. NUDCD2 represents a therapeutic target for conditions involving chr5 instability and developmental abnormalities.