KLHL7 (kelch like family member 7) functions as a substrate-specific adapter of the BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex, mediating Lys-48-linked ubiquitination and degradation of target proteins 1. In normal physiology, KLHL7 regulates terminal uridylyl transferase 1 (TUT1) ubiquitination, which is critical for maintaining nucleolar integrity 1. The protein is expressed in pluripotent cells, including human oocytes and embryonic stem cells, suggesting roles in early development 2. Pathogenic KLHL7 variants cause Perching syndrome, a rare autosomal recessive disorder characterized by multiple congenital contractures, microcephaly, blepharophimosis, and cleft palate, distinct from related Crisponi/cold-induced sweating syndrome 34. KLHL7 mutations are also associated with retinitis pigmentosa 42; disease-associated mutants fail to properly regulate TUT1 and nucleolar integrity, linking loss-of-function to photoreceptor degeneration 1. Beyond Mendelian disorders, KLHL7 is upregulated in malignancies including glioma and breast cancer, where it promotes cell viability and cycle progression via β-catenin pathway activation and glutamine metabolism enhancement 5. In breast cancer cohorts, high KLHL7 expression independently predicts poor prognosis and correlates with aggressive phenotype features 6, positioning it as a potential oncogenic driver and biomarker for malignant progression.