ATP2C1 and heart disorder: Previous studies have shown that small-molecule drugs targeting the lumen-facing cavity formed by TM2 and TM4–TM6 in NKAs are effective in treating heart diseases.52 In the early E2P structure of hSPCA1, we also observed a blob of EM density in the lumen-facing cavity, surrounded by Asp102 in TM2, Ala304 and Glu308 in TM4, Ile717 in TM5, Asn738, Asp742, and Gln747 in TM6, and Thr811 in TM8 (Supplementary information, Fig. S7a, b).