The secretory pathway kinases

•Phosphorylation of proteins and sugars in the secretory pathway is emerging as an important regulatory mechanism.•The Fam20C-and VLK-family of kinases mediate the phosphorylation of proteins in the secretory pathway and extracellular space.•Mutations in several secretory pathway kinases cause human disease

Protein phosphorylation is a nearly universal post-translation modification involved in a plethora of cellular events. Even though phosphorylation of extracellular proteins had been observed, the identity of the kinases that phosphorylate secreted proteins remained a mystery until only recently. Advances in genome sequencing and genetic studies have paved the way for the discovery of a new class of kinases that localize within the endoplasmic reticulum, Golgi apparatus and the extracellular space. These novel kinases phosphorylate proteins and proteoglycans in the secretory pathway and appear to regulate various extracellular processes. Mutations in these kinases cause human disease, thus underscoring the biological importance of phosphorylation within the secretory pathway. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases.