Although the exact thresholds for safely downregulating α-synuclein are still unknown, medical genetic insights and molecular and structural analyses of toxic alpha-synuclein aggregates, along with neuropathological evidence of alpha-synuclein accumulation in Lewy bodies, have supported the prevailing hypothesis that reducing alpha-synuclein levels may provide therapeutic advantages for PD and associated alpha-synucleinopathies (Sastre et al. 2023). The gene discussed is SNCA; the disease is synucleinopathy.