Does stromal interaction molecule-1 have five senses?

A single calcium (Ca2+ ) binding site within the canonical EF-hand loop was thought to govern the stromal interaction molecule-1 (STIM1) structural changes that lead to activation of Orai1 Ca2+ channels. Recent work by Gudlur et al., published in Nat Commun [9(1):4536], suggests that the STIM1 endoplasmic reticulum (ER) luminal domain has ∼5 additional Ca2+ binding sites, which underlie a surprising new proposal for Ca2+ sensing.