A working model of lactose synthesis in the Golgi apparatus demonstrates a possible role for TMEM165. To synthesize lactose, UDP-galactose is transported into the Golgi apparatus in exchange for luminal UMP by a nucleotide-sugar transporter (NST). A Mn2+-dependent lactose synthase (LS) covalently links the galactose to glucose, releasing a proton and UDP, the latter of which is cleaved by a Ca2+-dependent phosphatase (UDPase) into Pi and UMP. The Pi can complex with Ca2+, Mg2+, and casein and then be secreted into milk. Lactose drives osmotic uptake of water in the Golgi, secretory vesicles, and secreted milk to provide volume and reduce viscosity.