Table 1.

Relationship between confirmed familial PD genes and intracellular trafficking

Gene	Inheritancea	Clinicopathological phenotype	Function of the gene product	Refs
SNCA	AD	Early-onset, severe PD with Lewy Bodies	Interacts with SNARE proteins. Regulates neurotransmitter release and long-term synaptic homeostasis. Presynaptically enriched	20, 34
LRRK2	AD	Typical, late-onset PD with Lewy bodies	Has GTPase and kinase domains. Important roles in synaptic mechanics, endocytosis, and autophagy pathways	75, 80
GBA	AD	Typical, late-onset PD with Lewy bodies	Cleaves glucocerebroside during glycolipid metabolism. Interacts with α-synuclein in the lysosome	[86]
VPS35	AD	Typical, late-onset PD with unknown pathology	Role in endosome–Golgi complex trafficking; mutations impair autophagy.	[89]
Parkin	AR	Early-onset PD with slow progression and no Lewy bodies in most cases	Ubiquitin ligase that catalyses ubiquitin transfer to mitochondria for mitophagy	[82]
PINK1	AR	Early-onset PD with slow progression and Lewy body pathology	Has an essential role in mitophagy, and an emerging role in mitochondrial trafficking	81, 116
DJ-1	AR	Early-onset PD with slow progression and unknown pathology	Protects neurons against oxidative stress; some evidence for a role in autophagy	[117]
ATP13A2	AR	Juvenile-onset atypical parkinsonism (Kufor–Rakeb); pathology demonstrates ceroid lipofuscinosis	Encodes a lysosomal membrane transporter; mutations cause lysosome dysfunction and increased exosomal secretion of α-synuclein.	106, 118
PLA2G6	AR	Juvenile-onset atypical parkinsonism with brain iron accumulation	Encodes a calcium-independent phospholipase, which as a group have roles in membrane trafficking.	[119]
FBX07	AR	Juvenile-onset atypical parkinsonism with unknown pathology	Component of E3 ubiquitin protein ligases that participate in phosphorylation-dependent ubiquitination	[120]
DNAJC6	AR	Juvenile-onset atypical parkinsonism with unknown pathology	Involved in clathrin-mediated Golgi–lysosome trafficking and synaptic vesicle endocytosis.	93, 94
SYNJ1	AR	Juvenile-onset atypical parkinsonism with unknown pathology	Encodes synaptojanin-1, a presynaptically enriched protein involved in synaptic vesicle exocytosis	[91]

^aAD, autosomal dominant; AR, autosomal recessive.