MIDN (midnolin) is a ubiquitin-independent proteasomal adapter protein that facilitates degradation of stimulus-induced transcription factors including FOSB, EGR1, NR4A1, and IRF4 1. MIDN contains a ubiquitin-like domain that binds to proteasomal deubiquitinase RPN11, while its C-terminal α-helix simultaneously contacts RPN1, positioning substrates for translocation through the proteasome catalytic channel 1. This dual-binding mechanism allows MIDN to stimulate proteasome activity in a ubiquitin-independent manner 2. In the nervous system, MIDN promotes neurite outgrowth and regulates parkin E3 ligase expression through EGR1-dependent mechanisms 3 4. Notably, MIDN copy number loss is associated with Parkinson's disease in 10.5% of sporadic PD patients, establishing it as a genetic risk factor 3 5. In B lymphocytes, MIDN amplifies proteasome activity, supporting normal lymphopoiesis and enabling malignant B cell proliferation 2. MIDN dysregulation correlates with multiple cancer types, where it influences tumor progression through transcription factor degradation and immune cell infiltration patterns 6 7. These findings position MIDN as a critical regulator of cellular homeostasis with implications for neurodegenerative and malignant diseases.