There are six SGLT proteins identified in human,  Despite the prominent sequence homology between SGLT1 and SGLT2, they exhibit distinct physiological and biochemical properties. SGLT1 is primarily expressed in intestine, while SGLT2 is highly expressed in the kidney cortex and plays an important role in reabsorption of glucose in kidney. The major substrates of SGLT1 are both glucose and galactose, whereas SGLT2 prefers glucose to galactose. SGLT1 mutations are found in patients with glucose–galactose malabsorption. Mutations of SGLT2 are associated with the genetic disease Familial Renal Glucosuria. The characterizations of other SGLTs are rather preliminary. Interestingly, SGLT3 has no glucose transport activity, but may serve as a glucose sensor in the enteric nervous system. SGLT4 exhibits higher affinity for mannose than glucose and may function as a mannose transporter. SGLT5, which is highly expressed in kidney cortex, also has a substrate preference for mannose. SGLT6, also known as SMIT2 (myoinositol:Na1 symporter), transports inositol instead of glucose.


1.Deng D, et al. Protein Sci. 2016;25(3):546–558.