ATP13A2 is a lysosomal polyamine exporter functioning as a critical regulator of cellular homeostasis and neuronal integrity 1. The protein exhibits highest affinity for spermine among polyamines and facilitates their cytosolic export while promoting cellular polyamine uptake via endocytosis, protecting against polyamine-induced toxicity 1. Beyond polyamine transport, ATP13A2 maintains intracellular cation homeostasis, regulates zinc and manganese handling, and confers protection against heavy metal and mitochondrial stress. The protein coordinates lysosomal and mitochondrial maintenance through autophagy regulation, recruiting HDAC6 to deacetylate CTTN and promoting autophagosome-lysosome fusion 1. Loss of ATP13A2 function causes lysosomal rupture, cathepsin B activation, and compromised autophagy, mechanisms underlying neurodegeneration 1. ATP13A2 mutations cause Kufor-Rakeb syndrome, characterized by juvenile-onset parkinsonism with dementia, pyramidal degeneration, and supranuclear palsy 2. The gene is also implicated in atypical parkinsonism and neurodegeneration with brain iron accumulation (NBIA) 34. Disease-associated ATP13A2 mutations show functional impairment correlating with disease severity. Recent research highlights disturbed polyamine homeostasis as a key pathogenic mechanism in Parkinson's disease associated with ATP13A2 dysfunction 5.