KLHL13 (kelch like family member 13) functions as a substrate-specific adapter in the BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex, playing critical roles in cellular processes including mitosis, autophagy regulation, and pathogen responses. KLHL13 forms a functional E3 ubiquitin ligase complex with KLHL9 and CUL3 that mediates K63-linked ubiquitination of multiple substrates 12. This complex targets IRS1 for proteasomal degradation, where ATG16L1 deficiency leads to elevated KLHL9/KLHL13 expression and subsequent insulin resistance through IRS1 loss 3. In mitochondrial quality control, the KLHL9-KLHL13-CUL3 complex ubiquitinates IMMT at K211, initiating mitophagy to reduce mitochondrial ROS production 12. Pathogenic bacteria exploit this pathway, with Burkholderia pseudomallei's BipD protein hijacking the KLHL9-KLHL13-CUL3 complex to promote mitophagy for bacterial survival 12. KLHL13 also interacts with UBE2D3 to mediate K63-linked ubiquitination of TAP2, impairing antigen presentation and enabling cancer immune evasion 4. Clinically, KLHL13 shows altered expression in various diseases including AML, where RHOBTB2 stabilizes KLHL13 protein levels 5, and serves as a potential biomarker in idiopathic pulmonary fibrosis and osteosarcoma 67.