Model: endogenous FKBP12 limits use of rapamycin-induced translocation in DRG neurons but not HEK293 cells. A) In HEK293 cells, rapamycin promotes dimerization of membrane-tethered FRBPLF-CFP with Venus-FKBP12-Inp54p. Once at the membrane, Venus-FKBP12-Inp54p hydrolyzes PIP2 to PI(4)P. B) DRG neurons contain high levels of endogenous FKBP12 in the cytoplasm and, in some neurons, on the membrane. Rapamycin stabilizes FRBPLF-CFP (bold), but does not promote translocation of Venus-FKBP12-Inp54p to the membrane. These data suggest that rapamycin preferentially facilitates dimerization of FRBPLF-CFP with endogenous FKBP12 and occludes dimerization with Venus-FKBP12-Inp54p. Venus-FKBP12-Inp54p remains in the cytoplasm, unable to access PIP2 in the membrane.