Lipid Droplet‐Localized Spindle Apparatus Coiled‐Coil Protein 1 Regulates Lipid Droplet Distribution

ABSTRACT 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.