In neurons, the distribution of proteins within the plasma membrane (PM) is highly polarised. For instance, the cell-adhesion protein Caspr2 is enriched at juxtaparanodes of Ranvier in the axonal compartment, where it is necessary for the clustering of potassium channels such as Kv1.2. It is known that Kv1.2 is sorted selectively into axonal vesicles – but is Caspr2 targeted in tandem with Kv1.2? On page 3403, Catherine Faivre-Sarrailh and colleagues show that it is not. The authors first transfect hippocampal neurons with labelled Caspr2, and show that Caspr2 is present in the PM in axons, but that it colocalizes with early endosomes in the remainder of the cell (the somatodendritic compartment). Moreover, Caspr2 is eliminated from the PM at the somatodendritic compartment through dynamin-dependent endocytosis. The authors identify a short amino acid sequence (which contains a PKC substrate motif) within the cytoplasmic region of Caspr2 that is required for its endocytosis, and show that mutation of this motif, or chemical inhibition of PKC, disrupts the internalisation of Caspr2. Therefore, the authors conclude that PKC-regulated endocytosis of Caspr2 underlies its selective cell-surface expression, and that Caspr2 and Kv1.2 are targeted through distinct mechanisms. Their results underscore the diversity of mechanisms that maintain PM polarisation in neurons.