TPC2 activation regulates Ca ²⁺ entry in an agonist-selective manner. (a) Chemical structures of the TPC2 agonists TPC2-A1-N, its inactive analog SGA-10, TPC2-A1-P, and riluzole. Schematic depicts activation of TPC2-mediated Ca²⁺ flux by TPC2-A1-N and TPC2-mediated Na⁺ flux by TPC2-A1-P and riluzole. (b) Ca²⁺ signals (mean ± SEM, n = 3 independent biological replicates) in response to TPC2-A1-N (30 µM), TPC2-A1-P (30 µM), and a combination of the two. Parental cells were loaded with Fura-2 and stimulated in the absence of external Ca²⁺ using DMSO as a vehicle (Veh.) control. (c) Summary data (mean ± SEM, n = 3 independent biological replicates) quantifying the peak change in the Ca²⁺ signals. Each point represents the mean response from a cell population. *P < 0.05, ****P < 0.0001 (one-way ANOVA, Dunnett’s test). (d) Ca²⁺ signals (mean ± SEM, n = 3 independent biological replicates) in response to TPC2-A1-N (30 µM), TPC2-A1-P (30 µM), and a combination of the two. Parental cells were loaded with Fura-2 and stimulated in the presence of external Ca²⁺ using DMSO as a vehicle (Veh.) control. (e) Summary data (mean ± SEM, n = 3 independent biological replicates) quantifying the peak change in the Ca²⁺ signals. Each point represents the mean response from a cell population. *P < 0.05, **P < 0.01 (one-way ANOVA, Dunnett’s test). (f) Ca²⁺ signals (mean ± SEM, n = 4–9 independent biological replicates) in response to TPC2-A1-N (30 µM) or SGA-10 (30 µM) in combination with TPC2-A1-P (30 µM). Cells expressing wild-type or G2019S LRRK2 were loaded with Fura-2 and stimulated in the presence of external Ca²⁺. (g) Summary data (mean ± SEM, n = 4–9 independent biological replicates) quantifying the peak change in the Ca²⁺ signals in the indicated treatment and line. Each point represents the mean response from a cell population. **P < 0.01 (one-way ANOVA, Tukey’s test).