Not just protons: Chloride also activates lysosomal acidic hydrolases.

Lysosomal hydrolases require an acidic lumen for their optimal activities. In this issue, two independent groups (Wu et al. 2023. J. Cell Biol.https://doi.org/10.1083/jcb.202208155; Zhang et al. 2023. J. Cell. Biol.https://doi.org/10.1083/jcb.202210063) report that hydrolase activation also requires high intralysosomal Cl-, which is established by the lysosomal Cl-/H+ exchanger ClC-7.