SWS is the Drosophila member of the PNPLA6/NTE (neuropathy target esterase) family, best understood as an ER-membrane-associated phospholipase/esterase required for membrane lipid homeostasis and nervous-system integrity. Human NTE/PNPLA6 can rescue fly sws phenotypes, confirming true functional orthology.

PNPLA6/NTE and SWS are (lyso)phospholipases that preferentially hydrolyze phosphatidylcholine (PC) and lysophosphatidylcholine (LPC), with glycerophosphocholine (GPC) as a downstream product of PC/LPC deacylation, consistent with phospholipase B-like net activity on PC.

A key downstream product of PC/LPC deacylation by SWS/NTE is glycerophosphocholine (GPC).

SWS/PNPLA6 is primarily ER-localized, with ER anchoring mediated by the N-terminal transmembrane segment; the protein is enriched/primarily localized to ER membranes in flies.

SWS is functionally required in both neurons and multiple glial types, with especially strong recent evidence for a crucial role in surface/subperineurial glia that form the Drosophila blood-brain barrier.

Glial SWS is required for normal neuronal ensheathment and functional output; critically, rescue of glial knockdown locomotor phenotypes requires phospholipase activity, since phospholipase-dead SWS fails to rescue.

In sws mutants, increased PC and LPC pools support PC/LPC as physiological substrates/linked pathway metabolites, and altered ER membrane lipid composition promotes ER stress and downstream neurodegeneration.

A major 2024 development (Tsap et al., eLife) shows SWS/NTE is required in blood-brain-barrier-forming glia to maintain barrier structure and selective permeability, with loss producing a leaky BBB, lysosomal accumulations, and an age-dependent inflammatory response. NOTE: this BBB role is not yet captured in the existing GO annotations and the primary paper (Tsap 2024) is not cached, so no NEW annotation was added pending a verifiable primary reference.