Because (1) sortilin is the partner protein of the TREK-1 channel and (2) both proteins are colocalized in 5-HT-enriched areas known to be involved in the pathophysiology of depression such as the prefrontal and cingulate cortice, amygdala, hippocampus, nucleus accumbens, dorsal raphe, and hypothalamus [13], one may infer that spadin acts predominantly through a modulation of the brain 5-HT circuitry. Here, SORT1 is linked to major depressive disorder.