The endocannabinoid system (ECS) acts as a negative feedback mechanism to suppress synaptic transmission and plays a major role in a diverse range of brain functions including, for example, the regulation of mood, energy balance, and learning and memory. The function and dysfunction of the ECS are strongly implicated in multiple psychiatric, neurological, and neurodegenerative diseases. Cannabinoid type 1 receptor (CB1R) is the most abundant G protein-coupled receptor (GPCR) expressed in the brain and, as for any synaptic receptor, CB1R needs to be in the right place at the right time to respond appropriately to changing synaptic circumstances. While CB1R is found intracellularly throughout neurons, its surface expression is highly polarized to the axonal membrane, consistent with its functional expression at presynaptic sites. Surprisingly, despite the importance of CB1R, the interacting proteins and molecular mechanisms that regulate the highly polarized distribution and function of CB1R remain relatively poorly understood. Here we set out what is currently known about the trafficking pathways and protein interactions that underpin the surface expression and axonal polarity of CB1R, and highlight key questions that still need to be addressed. In the original article, we neglected to include the funders BBSRC, (BB/R00787X/1) to JH and KWandWellcome Trust, (105384/Z/14/A) to JH and AE. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. © 2020 Fletcher-Jones, Hildick, Evans, Nakamura, Henley and Wilkinson.< Réduire