CAPN6 is a non-proteolytic calpain family member that functions as a microtubule-stabilizing protein and regulator of cytoskeletal dynamics 1. Unlike classical calpains, CAPN6 lacks active-site cysteine residues and does not possess protease activity 2. CAPN6 stabilizes microtubules by forming acetylated α-tubulin-rich bundles and regulates cell movement through Rac1/ARHGEF2-mediated lamellipodial formation 1. The PI3K-Akt signaling pathway regulates CAPN6 expression at transcriptional and post-transcriptional levels 2. CAPN6 has important roles in developmental and pathological contexts. CAPN6 deficiency promotes skeletal muscle differentiation during both embryonic development and adult regeneration 3. Conversely, CAPN6 overexpression promotes tumor progression in multiple contexts: it enhances uterine leiomyoma cell proliferation while suppressing apoptosis via Rac1/PAK1 signaling 4, is overexpressed in all uterine sarcomas and carcinosarcomas 5, and is upregulated in osteosarcoma and other tumors via PI3K/Akt pathway activation 6. In atherosclerosis, CAPN6 induction in inflamed macrophages dysregulates pre-mRNA splicing by sequestering CWC22, suppressing Rac1 signaling and promoting lipid accumulation 7. CAPN6 overexpression also drives chrX kidney disease progression through NF-κB-dependent mechanisms 8. These findings establish CAPN6 as a potential therapeutic target for cancer, atherosclerosis, and kidney disease.