Procollagen 1 assembles into phase-separated condensates in the endoplasmic reticulum.

Procollagen I (PC1) is assembled into a trimer within the lumen of the endoplasmic reticulum (ER). In vitro, collagen trimers form rigid molecules reaching lengths of up to 400 nm, and this conformation is presumed to represent their assembled state in vivo. Here, we demonstrate that endogenous PC1 assembles into biomolecular condensates in the ER of activated human hepatic stellate cells. PC1 condensates form in response to increased collagen synthesis and are part of a multicomponent system enriched in the chaperones Hsp47 and calreticulin, as well as the disulfide isomerases PDIA1 and PDIA6, but notably lacking the unfolded protein sensor BiP. PC1 condensates localize to ER exit sites, a process mediated by TANGO1, and dissipate upon ER stress. We propose that this organization enables the accommodation of large quantities of PC1 in the ER lumen without triggering degradation. Furthermore, we suggest that PC1 within condensates is exported in a manner resembling liquid extrusion rather than as a rigid trimer.