In addition to fecal and bacterial choline depletion, impaired endogenous (indirect) choline synthesis by methylation of phosphatidylethanolamine (PE), which requires SAM and PE-N-methyltransferase (PEMT), may contribute to choline deficiency in EPI of CF patients: while the PEMT pathway is generally decreased in these patients [6], frequent single nucleotide polymorphisms (SNPs) of the PEMT gene (such as rs12325817; 25–44% of the population) [22] may further impact the severity of the clinical consequences of choline deficiency. Here, PEMT is linked to cystic fibrosis.