TABLE 1:

Current genetically encoded lipid biosensors for a variety of selective lipid species.

Lipid	Biosensor	Affinity	Lipid specific?	Cellular localization of lipid		References
				Lipid dependent?	Lipid sufficient?
Chol	D4-PFO + mutants	2–30 mol%	✔	✔	?	Shimada et al., 2002; Maekawa and Fairn, 2015; Liu et al., 2016
SM	Lysenin	Kd ∼ 5 nM	✔	✔	?	Yamaji et al., 1998; Kiyokawa et al., 2005; Abe et al., 2012
PA	NES-PABD-spo20p51–91 (PASS)	?	✘ - binds PI(4,5)P2 and PIP3 weakly	✔	?	Zhang et al., 2014
	NES-2xPABD-spo20p51–91	?	✘ - suspected to bind PI(4,5)P2 and PIP3 weakly	✔	?	Bohdanowicz et al., 2013
	α-Syn-N	Kd ∼ 6.6 μM (18:1/18:1 PA)	✔	✔	?	Yamada et al., 2020
PS	C2-lactadherin	Kd ∼ 0.5 µM	✔	✔	✔	Yeung et al., 2008; Maeda et al., 2013; Vecchio and Stahelin, 2018
DAG	C1ab-PDK1	Ki (PDBu) ∼ 0.2 µM	✔	✔	✔	Chen et al., 2008; Kim et al., 2011
	C1ab-PKCε	Kd ∼ 10 nM	✔	✔	?	Stahelin et al., 2005; Domart et al., 2012
PI	BcPI-PLCH82A	?	✘ - binds to PC	✔	✔	Pemberton et al., 2020
	BcPI-PLCANH	?	✘ - binds DAG	✔	✔	Pemberton et al., 2020
PI4P	P4M-SidM	Kd ∼ 1 µM or ∼18.2 nM FL	✔	✔	✔	Brombacher et al., 2009; Schoebel et al., 2010; Hammond et al., 2014
	P4M-SidMx2	Kd < P4M-SidM	✔	✔	✔	Hammond et al., 2014; Levin et al., 2017
	P4C-SidC	Kd ∼ 250 nM	✔	✔	✔	Dolinsky et al., 2014; Weber et al., 2014; Zewe et al., 2018
	N-PH-ORP5, N-PH-ORP8	Kd ∼ 5 µM for PI(4,5)P2	✘ - binds PI4P and PI(4,5)P2	✔	✘ - requires PI(4,5)P2	Chung et al., 2015; Ghai et al., 2017; Sohn et al., 2018
	PH-OSBP, PH-FAPP1	Kd ∼ 250 nM	✘ - binds PI(4,5)P2	✔	✘ - requires Arf1	Levine and Munro, 2002; Szentpetery et al., 2010; Lenoir et al., 2015
PI5P	3xPHD (ING2)	?	✘ - binds to PI3P	✔	✔	Gozani et al., 2003; Pendaries et al., 2006
PI(4,5)P2	PH-PLCδ1	Kd ∼ 2 µM	✘ - binds to IP3∼20-fold more tightly than PI(4,5)P2	✔	✔	Garcia et al., 1995; Lemmon et al., 1995; Stauffer et al., 1998; Várnai and Balla, 1998; Hirose et al., 1999; Suh et al., 2006
	PH-PLCδ4	Kd > PH-PLCδ1	✘ - binds to IP3	✔	✔	Lee et al., 2004; Hammond and Balla, 2015
	Tubbyc	Kd > PH-PLCδ1	✘ - binds PI(3,4)P2 and PI(3,4,5)P3	✔	✔	Quinn et al., 2008; Szentpetery et al., 2008; Halaszovich et al., 2009; Hammond and Balla, 2015
	TubbycR332H	Kd > Tubby	✘ - binds PI(3,4)P2 and PIP3	✔	?	Quinn et al., 2008
	ENTH/ANTH	Kd ∼ 2 µM	✘ - binds to PIP3	✔	?	Ford et al., 2001; Itoh et al., 2001; Yoon et al., 2011
PI3P	FYVE-Hrsx2	Kd ∼ 2.5 µM	✔	✔	?	Burd and Emr, 1998; Gaullier et al., 1998; Gillooly et al., 2000; Sankaran et al., 2001
	FYVE-EEA1	Kd ∼ 45 nM	✔	✔	?	Burd and Emr, 1998; Gaullier et al., 1998, 2000
	PX-p40phox	Kd ∼ 5 µM	✔	✔	?	Bravo et al., 2001; Ellson et al., 2001; Kanai et al., 2001
PI(3,5)P2	ML1-Nx2	Kd ∼ 5.6 µM	✔	✔/✘a	✔/✘a	Li et al., 2013; Hammond et al., 2015
PI(3,4)P2	PH-TAPP1-CT	Kd ∼ 80 nM	✔	✔	✔	Dowler et al., 2000; Thomas et al., 2001; Kimber et al., 2002; Marshall et al., 2002; Manna et al., 2007
	eTapp1-PHc	Kd ∼ 80 nM	✔	✔	✔	Liu et al., 2018
	TAPP1-cPHx3	Kd > 80 nM	✔	✔	✔	Goulden et al., 2019
PIP3	PH-ARNO2G-I303Ex2	Kd ∼ 170 nM	✘ - binds IP4	✔	✔	Goulden et al., 2019
	eMyoX-PHx2c	Kd ∼ 33 nMb	✘ - binds IP4	✔	✔	Hokanson et al., 2006; Plantard et al., 2010; Lu et al., 2011; Liu et al., 2018
	PH-Akt	Kd ∼ 590 nM	✘ - binds PI(3,4)P2 and IP4	✔	?	Frech et al., 1997; Watton and Downward, 1999; Manna et al., 2007
	PH-Btk	Kd ∼ 80 nM	✘ - binds IP4	✔	?	Fukuda et al., 1996; Salim et al., 1996; Rameh et al., 1997; Kontos et al., 1998; Manna et al., 2007
	PH-GRP1 (2G), PH-ARNO (2G)	Kd ∼ 170 nM	✘ - binds IP4	✔	✘ - binds Arf/Arl	Klarlund et al., 1997; Venkateswarlu et al., 1998; Gray et al., 1999; Cohen et al., 2007; Hofmann et al., 2007; Li et al., 2007; Manna et al., 2007

^aThe accuracy of this probe is disputed.

^bThe K_d value is derived from myosin-c tail and IP₄ headgroup binding.

^cRequires chemical ligation with a solvatochromic dye for optimal performance.