SCYL1 deficiency in CALFAN syndrome is associated with ER stress and cell death.

ABSTRACT: CALFAN syndrome is a rare genetic disorder affecting the nervous system and liver, with skeletal abnormalities also reported. It is caused by mutations in SCYL1, a gene encoding a ubiquitously expressed protein localized to the secretory pathway. SCYL1 interacts with trafficking components, including ARF GTPases and the COPI vesicle coat complex, and appears to function in retrograde secretory trafficking. Despite this knowledge, the mechanisms that underlie CALFAN pathology remain poorly understood. Here, using fibroblasts obtained from patients diagnosed with CALFAN syndrome and from SCYL1 knockout fibroblasts, we reveal an accumulation of the abundant secretory cargo procollagen type I in the endoplasmic reticulum (ER) upon SCYL1 deficiency. Surprisingly, we failed to observe procollage

SUBMITTER: Hellicar J 

PROVIDER: S-EPMC12690549 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature