Slc35b2, also known as PAPST1, is a Golgi-resident transporter responsible for transporting the sulfate donor 3'-phosphoadenosine 5'-phosphosulfate. This function is crucial for protein tyrosine sulfation (PTS) and sulfated proteoglycan biosynthesis, processes involved in multiple biological pathways. It has been implicated in various physiological and pathological processes, highlighting its overall biological importance. Genetic models, such as gene knockout mouse models, have been valuable in studying its functions [1-3, 5-10].

Knocking down Slc35b2 in HCC cells led to inhibited tumor growth both in vivo and in vitro. This was due to the disruption of the SLC35B2/SAV1 sulfation axis, which normally inhibits Hippo signaling under oxidative stress [1]. In patients with chondrodysplasia and hypomyelinating leukodystrophy, homozygous variants in Slc35b2 were found, affecting its mRNA expression, protein subcellular localization, and ultimately causing proteoglycan sulfation impairment [2]. In EV71 infection, knockout of Slc35b2 decreased the binding and internalization of the virus into cells, as it plays a dual role in regulating host cell sulfation [3]. In pancreatic ductal adenocarcinoma, knocking down Slc35b2 inhibited cell proliferation and migration in vitro and tumor growth and metastasis in vivo, likely by destabilizing integrin β4 [4].

In conclusion, Slc35b2 is essential for sulfation-related biological processes. Studies using gene knockout models have revealed its role in diseases such as HCC, chondrodysplasia with hypomyelinating leukodystrophy, EV71 infection, and pancreatic ductal adenocarcinoma. Understanding Slc35b2's functions through these models provides insights into disease mechanisms and potential therapeutic targets.