While dysregulation of S100 proteins are implicated in heart failure, recent research has revealed broader mechanistic links: specific S100 proteins are now recognized for their emerging roles in modulating mitochondrial homeostasis (Wang et al., 2024; Wu et al., 2023; Pei et al., 2024; Zhang et al., 2023) and mTOR signaling (Fan et al., 2023; Teng et al., 2021; Zhou et al., 2024), highlighting functions that extend beyond cardiovascular pathology. Here, MTOR is linked to heart failure.