ISG15 and major depressive disorder: Motor learning deficit on rotarod by 5–6 weeks, memory issues by ~8 weeks, non-motor signs (anxiety, depression-like behavior) manifest by 2–6 months alongside neuropathology. Biochemical and molecular parameters: composition and dynamics of ATXN1 nuclear inclusions, protein (interactome) and RNA (transcriptome, splicing) interaction profiles (innate immune IFN-ISG15 activation by 6–8 weeks, elevated glutamine & creatine on MRS). Neuronal inclusions appear by 6 months, correlating with later-stage degeneration; more robust weight reduction ~32 weeks.