LD biogenesis is initiated in the ER. Nascent LDs harboring seipin at their ER contact recruit proteins and lipids from the ER to promote LDgrowth. LDs remain associated with the ER during maturation, allowing continuous cargo exchange between these compartments. In seipin deficient cells, ER-LD contacts are morphologically abnormal, either missing, rudimentary or aberrantly extensive. Most newly formed LDs lack functional contacts with the ER. HPos, a model ER-to-LD targeting peptide can initially reach LDs but its access to LDs is later perturbed. ACSL3, a lipid biosynthetic enzyme normally targeted to the LD surface remains in the ER or at ER-LD junctions. Oleic acid flux into neutral lipids is initially intact but subsequently impaired. In contrast, ADRP, a cytoplasmic coat protein, reaches LDs independently of seipin. Defective ER-LD contacts result in discontinued cargo exchange and arrested LD maturation, where the majority of LDs fail to grow beyond the diameter of ~200 nm. 