NSFL1C (NSFL1 cofactor, also known as p47) is a VCP cofactor that regulates multiple cellular processes critical for mitotic progression and neurodegeneration. Functionally, NSFL1C reduces VCP ATPase activity and is necessary for Golgi stack fragmentation during mitosis and reassembly afterward 1. It regulates centrosomal Aurora A (AURKA) levels during mitosis by promoting removal from centrosomes in prophase and controls spindle orientation 1. NSFL1C functions within a PINK1-VCP-PKA signaling pathway where PINK1 phosphorylates p47 at S176 to promote dendritic arborization and spinogenesis in neurons 23. In tau seeding pathways relevant to tauopathies, NSFL1C reduction decreases tau seed amplification within 5 hours of exposure, suggesting VCP-NSFL1C complexes direct pathological tau toward degradation rather than replication 45. NSFL1C also regulates autophagy flux and lysosomal homeostasis; p47 ablation increases HER2+ breast cancer metastasis by impairing lysosomal damage repair and NEMO trafficking 6. Clinically, reduced NSFL1C expression correlates with increased metastasis and decreased survival in breast cancer patients 6. Additionally, NSFL1C loss suppresses spindle assembly checkpoint activation in BRCA2-deficient prostate cancer, promoting cell survival 7.