ERICH3 (glutamate rich 3) is a multifunctional protein with distinct roles in ciliary biology and neuronal serotonin homeostasis. As a primary cilium component, ERICH3 regulates cilium formation and length by functioning within retrograde intraflagellar transport (IFT) pathways to remove signaling proteins from cilia 1. Loss of ERICH3 results in abnormally short cilia and accumulation of IFT proteins at the ciliary tip, while also causing dysregulation of sonic hedgehog signaling molecules 1. Additionally, ERICH3 plays a critical role in neuronal vesicle biogenesis and serotonergic neurotransmission. The protein colocalizes with serotonin in vesicle-like structures and interacts with clathrin heavy chain, a key vesicular trafficking component 2. ERICH3 knockout dramatically decreases serotonin concentrations in neuronal cells 2. Clinically, ERICH3 variants are associated with SSRI treatment response in major depressive disorder patients across multiple independent trials 234. Baseline and changes in plasma serotonin concentrations—both associated with ERICH3 genetic variation—predict SSRI remission outcomes 5. Furthermore, enterovirus 71 VP1 protein promotes serotonin release by upregulating ERICH3 expression 6, suggesting its involvement in infection-related neurological complications.