C57BL/6JCya-Retreg1^em1flox/Cya

RETREG1, also known as FAM134B, is a reticulophagy receptor. Reticulophagy is a selective process that removes impaired endoplasmic reticulum (ER) subdomains through autophagy-mediated lysosomal degradation, and RETREG1 plays a crucial role in maintaining ER homeostasis [1,2]. It is also involved in various biological processes and human diseases [2].

Loss-of-function mutations in the RETREG1 gene result in Hereditary Sensory Autonomic Neuropathy Type 2B. Clinical features include pain loss, autonomic disturbances, and upper motor neuron features [3]. In cancer, it acts as a tumor suppressor and its mutations are common in patients with colorectal adenocarcinoma and oesophageal squamous cell carcinoma, associated with the biological aggressiveness of these cancers [2]. Some viruses, like Dengue, Zika, and West Nile virus, can selectively cleave FAM134B, leading to increased production of infection units, while its upregulation inhibits viral replication [2].

In conclusion, RETREG1 is essential for maintaining ER homeostasis through its role in reticulophagy. Studies of RETREG1-related gene knockout models have revealed its significant contributions to understanding the pathogenesis of hereditary sensory autonomic neuropathy and its potential role in cancer and viral-related diseases, providing insights into disease mechanisms and potential therapeutic targets.