(A) In lung alveoli at homeostasis, lamellar bodies may be found fused with AT2 cell plasma membranes or unfused, and as single vesicles or in chains or clusters. TMEM63 ion channels located on lamellar body membranes might sense AT2 cell stretch through a mechanism termed “force-from-lipids,” in which AT2 cell plasma membrane strain is conveyed to TMEM63 via sites of plasma and lamellar body membrane fusion. Alternatively, or in addition, lamellar bodies may experience what is known as “force-from-filament” mechanotransduction, in which strain is conveyed via plasma membrane–attached cytoskeletal filaments. Chen, Li, and co-authors (9) propose a three-part mechanism by which TMEM63 links inflation-induced alveolar strain to surfactant secretion: (i) stretch-induced activation of cation currents by TMEM63A and TMEM63B causes (ii) lamellar body ATP release and (iii) autocrine ATP signaling, leading to a cytosolic Ca²⁺ increase and surfactant secretion. (B) The findings by Chen, Li, and co-authors (9) also suggest that inflation-induced alveolar strain activates TMEM63-mediated cation currents in AT1 cells. Such currents might initiate signaling pathways that regulate alveolar barrier function or promote surfactant secretion in neighboring AT2 cells through, for example, gap junctional communication.