Lipid Droplet-Localized Spindle Apparatus Coiled-Coil Protein 1 Regulates Lipid Droplet Distribution.

Lipid droplets (LDs) are central to cellular energy homeostasis and lipid metabolism. While LD-associated proteins are known to regulate LD dynamics and function, their roles in LD transport and their broader cellular significance remain poorly understood. In this study, we identify lipid droplet-localized spindle apparatus coiled-coil protein 1 (SPDL1-L) as a key regulator of intracellular LD transport. SPDL1-L localizes to LDs through the synergistic action of its hydrophobic region and nearby basic residues. SPDL1-L expression promotes LD clustering at the microtubule-organizing center (MTOC) and the formation of donut-shaped (toroidal) nuclei during cell division. SPDL1-L-mediated LD clustering is likely through dynein-mediated minus end transport. LD clustering activity is diminished when the LD targeting or dynein binding function of SPDL1-L is impaired. Together, our findings provide new insights into the mechanisms governing LD dynamics and their impact on cellular organization.