The cream fraction of milk comprises droplets of triacylglycerol coate
d with cellular membranes. In this review, we discuss how these drople
ts are formed and secreted from mammary epithelial cells during lactat
ion. This secretory system is especially interesting because the assem
bled lipid droplets are secreted from the cytoplasm enveloped by cellu
lar membranes. In other cells, such as hepatocytes and enterocytes, li
pid is secreted by exocytosis from membrane-bounded compartments of th
e secretory pathway. Milk lipids originate as small droplets of triacy
lglycerol, synthesized in or on the surfaces of rough endoplasmic reti
culum (ER)(4) membranes. These droplets are released into the cytoplas
m as microlipid droplets (MLDs) with a surface coat of protein and pol
ar lipid. MLDs may fuse with each other to form larger cytoplasmic lip
id droplets (CLDs). Droplets of varying size, are transported to the a
pical cytoplasm by unknown mechanisms and are secreted from the cell c
oated with an outer bilayer membrane. CLDs may increase in size in all
regions of the cell, especially at the plasma membrane during secreti
on. Two possible mechanisms for lipid secretion have been proposed: an
apical mechanism, in which lipid droplets are enveloped with apical p
lasma membrane, and a secretory-vesicle mechanism, in which fat drople
ts are surrounded by secretory vesicles in the cytoplasm and are relea
sed from the surface by exocytosis from intracytoplasmic vacuoles. A c
ombination of both mechanisms may be possible. Following secretion, a
fraction of the membrane surrounding the globules may be shed from the
droplets and give rise to membrane fragments in the skim milk phase.