The mechanism underlying the effects of rs707922 on plasma TC and LDL-C levels in diabetes remains elusive. Richter et al., reported HNF-1 alpha being a potent transcription activator of APOM [28] . The decreased serum apoM level in maturity-onset diabetes of the young subjects as compared to the controls could be explained by the HNF-1 alpha mutations in these patients [28] . Given the association between APOM and metabolic traits found in this study, one may speculate that SNP rs707922 (G+1837T), in the capacity of an intronic SNP (reference to the APOM1 transcript), may modify APOM expression through SNP-specific recruitment of transcription factors (i.e., PAX 6 showed an allelespecific interaction with rs707922 T by computer prediction as presented in Supplementary Figure S5 ) and subsequently affect cellular cholesterol homeostasis in liver and possibly other tissues. More interestingly, we found that rs707922 can also assume the capacity as an exonic SNP (i.e., reference to the APOM5 transcript). While the function of APOM5 requires further elucidation, the high renal and hepatic expression levels of APOM1 and APOM5 indicated the possibility of these transcripts coordinate to regulate cholesterol homeostasis in these tissues. Such possibility is further supported by the results showing the activities of ectopically expressed APOM5 in modifying hepatic cell cholesterol content. With regards to systematic cholesterol homeostasis, we observed that homozygous rs707922-T allele associated with elevated total-and LDL-cholesterol levels. One possible mechanism of such elevation is through reducd hepatic and/or pheripheral clearance of circulating cholesterol. Consistent with this notion, our in vitro data showed that hepatic cells overexpressing APOM5-T transcript had lower cholesterol content relative to cells expressing the APOM5-G counterpart.