Although TBC1D5 can modulate Rab7a activity, it is not the only reported GTPase-activating protein for Rab7a as both TBC1D15 and the Rac1 effector Armus have been reported to function as GAPs for Rab7a (Zhang et al., 2005; Frasa et al., 2010). Hence, it is possible that some of the potential negative consequences of the loss of TBC1D5 could be mitigated by compensatory effects mediated through TBC1D15 and Armus. While this article was in preparation, a study from Steinberg and colleagues reported that loss of TBC1D5 function results in a hyper-activated Rab7a (Jimenez-Orgaz et al., 2018), which demonstrates increased binding to RILP, a Rab7a effector. Our results broadly agree with theirs in that we observe an increase in activated Rab7a after loss of TBC1D5 expression along with enhanced association of Rab7a with an effector, namely the retromer CSC. Our data is also in agreement with the study from Steinberg and colleagues with respect to effects on the trafficking of retromer cargo proteins such as Glut1 but their study was focused on the effect of increased Rab7a activity on mitophagy – the
