Single-cell profiling studies and research on both postmortem PD tissues and preclinical mouse models demonstrated that Sox6/Aldh1a1 markers molecularly define the vulnerable ventral tier dopamine neurons,11,12 while Calbindin1 (Calb1) marks the resilient dorsal tier neurons (Figure 1A).1,44 These distinct dopamine neuronal subtypes differ in their molecular profiling; they also exhibit unique projection patterns and functional responses.10,13,17 Therefore, studying these neurons in a subtype-specific manner can yield important insights into cell-intrinsic mechanisms of vulnerability in PD. This evidence concerns the gene ALDH1A1 and Parkinson disease.