Phosphatidylcholine biosynthesis in animal cells is primarily regulated by the rapid translocation of CTP:phosphocholine cytidylyltransferase alpha between a soluble form that is inactive and a membrane-associated form that is activated. Until less than 10 years ago there was no information on the transcriptional regulation of phosphatidylcholine biosynthesis. Research has identified the transcription factors Sp1, Rb, TEF4, Ets-1 and E2F as enhancing the expression of the cytidylyltransferase and Net as a factor that represses cytidylyltransferase expression. Key transcription factors involved in cholesterol or fatty acid metabolism (SREBPs, LXRs, PPARs) do not have a major role in transcriptional regulation of the cytidylyltransferase. Rather than being linked to cholesterol or energy metabolism, regulation of the cytidylyltransferase is linked to the cell cycle, cell growth and differentiation. Transcriptional regulation of phospholipid biosynthesis is more elegantly understood in yeast and involves responses to inositol, choline and zinc in the culture medium.